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Home> Encyclopedia >   /  Antibiotic and antimicrobial agents  /  Pharmaceutical Intermediates  /  Hormones and synthetic substitutes
Norethindrone structure
Norethindrone structure

Norethindrone

Iupac Name:(8R,9S,10R,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,9,10,
11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
CAS No.: 68-22-4
Molecular Weight:298.41924
Modify Date.: 2022-11-29 06:34
Introduction: Progestin contraceptives work by producing pregnant-like conditions in a female to preventovulation.During pregnancy, progesterone is released by the placenta during development ofthe fetus.This in turn suppresses development of egg follicles and ovulation. Progestins mimicthis condition and thus prevent or delay ovulation.Oral contraceptives currently use progestinand estrogen in combination to prevent ovulation and thicken cervical mucus.The latter makeit harder for sperm to enter the uterus and for an egg to implant on the uterine wall. View more+
1. Names and Identifiers
1.1 Name
Norethindrone
1.2 Synonyms

(17a)-17-Hydroxy-19-norpregn-4-en-20-yn-3-one (17b)-17-ethynyl-17-hydroxyestr-4-en-3-one (17α)-17-Hydroxy-19-norpregn-4-en-20-yn-3-one (8R,9S,10R,13S,14S,17R)-17-éthynyl-17-hydroxy-13-méthyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tétradécahydro-3H-cyclopenta[a]phénanthrén-3-one (8R,9S,10R,13S,14S,17R)-17-Ethinyl-17-hydroxy-13-methyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-on (8R,9S,10R,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one 17a-ethynyl-19-nortestosterone 17ALPHA-ETHYNYL-17BETA-HYDROXY-19-NOR-4-ANDROSTEN-3-ONE 17ALPHA-ETHYNYL-19-NORTESTOSTERONE 17-Hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one 17α-Ethynyl-17-hydroxy-4-estren-3-one 17α-Ethynyl-17Β-hydroxy-19-norandrost-4-en-3-one 17α-Ethynyl-17Β-hydroxyestr-4-en-3-one 17α-Ethynyl-19-nortestosterone 17Β-Hydroxy-19-norpregn-4-en-20-yn-3-one 19-Nor-17a-ethynyl-17b-hydroxy-4-androsten-3-one 19-Nor-17a-ethynylandrosten-17b-ol-3-one 19-Nor-17a-ethynyltestosterone 19-NOR-17ALPHA-ETHYNYL-4-ANDROSTEN-17BETA-OL-3-ONE 19-Nor-17-ethinyl testosterone 19-nor-17α-Ethynyl-17Β-hydroxy-4-androsten-3-one 19-nor-17α-Ethynylandrosten-17Β-ol-3-one 19-Nor-17α-ethynyltestosterone 19-Nor-17α-pregn-4-en-20-yn-3-one, 17-hydroxy- 19-NOR-4-ANDROSTEN-17-ALPHA-ETHYNYL-17-BETA-OL-3-ONE 19-NOR-4-ETHISTERONE 19-NORETHINDRONE 19-NORETHISTERONE 19-Norpregn-4-en-20-yn-3-one, 17-hydroxy-, (17α)- 19-Nortestosterone, 17-ethynyl- Anovule EINECS 200-681-6 ENT estr-4-en-3-one, 17-ethynyl-17-hydroxy-, (17b)- Estr-4-en-3-one, 17-ethynyl-17-hydroxy-, (17Β)- Estr-4-en-3-one, 17α-ethynyl-17-hydroxy- Ethinylnortestosterone Ethynylnortestosterone Gestest Menzol MFCD00067596 Mini-Pe NET Norethindrone (USP) norethisterone Norfor Norgestin Noriday Norpregneninolone Primolut N sc4640 Triella Utovlan

1.3 CAS No.
68-22-4
1.4 CID
6230
1.5 EINECS(EC#)
200-681-6
1.6 Molecular Formula
C20H26O2 (isomer)
1.7 Inchi
InChI=1S/C20H26O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,12,15-18,22H,4-11H2,2H3/t15-,16+,17+,18-,19-,20-/m0/s1
1.8 InChkey
VIKNJXKGJWUCNN-XGXHKTLJSA-N
1.9 Canonical Smiles
CC12CCC3C(C1CCC2(C#C)O)CCC4=CC(=O)CCC34
1.10 Isomers Smiles
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=CC(=O)CC[C@H]34
2. Properties
3.1 Density
1.15
3.1 Melting point
205-206℃
3.1 Boiling point
447 °C at 760 mmHg
3.1 Refractive index
1.577
3.1 Flash Point
447 °C at 760 mmHg
3.1 Precise Quality
298.19300
3.1 PSA
37.30000
3.1 logP
3.49250
3.1 Solubility
7.043mg/L(25 ºC)
3.2 Appearance
white to off-white powder
3.3 Carcinogenicity
Norethisterone is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. Norethindrone Preparation Products And Raw materials Raw materials
3.4 Chemical Properties
Off-White to Pale Yellow Solid
3.5 Color/Form
Powder
3.6 Decomposition
When heated to decomposition, it emits acrid smoke and fumes.
3.7 Odor
ODORLESS
3.8 pKa
13.09±0.40(Predicted)
3.9 Water Solubility
chloroform: ≥50?mg/mL, clear, colorless
3.10 Spectral Properties
Specific optical rotation: -31.7 @ 20 deg C/D (chloroform); first reported as -25 @ 20 deg C/D (chloroform); max absorption (ethanol): 240 nm (log e= 4.24)
3.11 Stability
Stable in air.
3.12 StorageTemp
2-8°C
3. Use and Manufacturing
4.1 Definition
ChEBI: A 17beta-hydroxy steroid that is testosterone in which the hydrogen at position 17 is replaced by an ethynyl group and in which the methyl group attached to position 10 is replaced by hydrogen.
4.2 History
The development of norethindrone as a female oral contraceptive took place indirectly over 30 years as a result of steroid research.This research accelerated in the 1930s when structures and medical applications of steroidal compounds were determined.Steroids are lipids, which include cholesterol, bile salts,and sex hormones,that are characterized by a structure of three fused six-carbon rings and a five-carbon ring. In 1957, both norethindrone and norethynodrel were approved by the Food and Drug Administration (FDA) for treating menstrual problems and infertility. In 1960, the FDA approved Searle's norethynodrel under the trade name Enovid. Norethindrone was approved as an oral contraceptive in 1962 under the trade name Ortho-Novum.
4.3 Usage
Progestin contraceptives work by producing pregnant-like conditions in a female to preventovulation.During pregnancy, progesterone is released by the placenta during development ofthe fetus.This in turn suppresses development of egg follicles and ovulation. Progestins mimicthis condition and thus prevent or delay ovulation.Oral contraceptives currently use progestinand estrogen in combination to prevent ovulation and thicken cervical mucus.The latter makeit harder for sperm to enter the uterus and for an egg to implant on the uterine wall.
4. Safety and Handling
5.1 Symbol
GHS08
5.1 Hazard Codes
Xn
5.1 Signal Word
Warning
5.1 Risk Statements
R40
5.1 Safety Statements
22-36/37/39-45-26
5.1 Exposure Standards and Regulations
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
5.2 Octanol/Water Partition Coefficient
log P = 2.97
5.3 Hazard Declaration
H351
5.3 DisposalMethods
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
5.4 RIDADR
UN 3077 9 / PGIII
5.4 Safety Profile
Confirmed carcinogenwith experimental carcinogenic,tumorigenic, and teratogenic data. Mddlytoxic by ingestion. Human systemic effectsby ingestion: dermatitis and androgeniceffects. Human teratogenic effects:developmental abnormalities of themusculoskeletal system and urogenitalsystem; and behavioral effects in thenewborn. Human reproductive effects:spermatogenesis; testes, epididymis, spermduct changes; impotence; male breastdevelopment; other male effects; ovaries,fallopian tube changes; menstrual cycle effects; postpartum effects; changes infemale fertility. Experimental reproductiveeffects. Human mutation data reported.When heated to decomposition it emitsacrid smoke and irritating fumes.
5.5 Caution Statement
P281
5.5 Formulations/Preparations
Norethisterone is available in the US as a grade containing 97-102% ai on an anhydrous basis.
NORETHINDRONE, USP (MICRONOR, NOR-QD, NORLUTIN), & NORETHINDRONE ACETATE, USP (NORLUTATE), ARE AVAIL ALONE IN 0.35-5-MG TABLETS & IN COMBINATION WITH ESTROGENS AS ORAL CONTRACEPTIVES.
5.6 WGK Germany
3
5.6 RTECS
RC8975000
5.6 Report
NTP 10th Report on Carcinogens. IARC Cancer Review: Animal Sufficient Evidence IMEMDT ?? IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man . 7 ,1987,p. 294.(World Health Organization, Internation Agency for Research on Cancer,Lyon, France.:?) (Single copies can be ordered from WHO Publications Centre U.S.A., 49 Sheridan Avenue, Albany, NY 12210) . EPA Genetic Toxicology Program.
Safety Profile

Confirmed carcinogen with experimental carcinogenic, tumorigenic, and teratogenic data. Mildly toxic by ingestion. Human systemic effects by ingestion: dermatitis and androgenic effects. Human teratogenic effects: developmental abnormalities of the musculoskeletal system and urogenital system; and behavioral effects in the newborn. Human reproductive effects: spermatogenesis; testes, epididymis, sperm duct changes; impotence; male breast development; other male effects; ovaries, fallopian tube changes; menstrual cycle changes or disorders; uterus, cervix, vagina effects; postpartum effects; changes in female fertility. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

5.7 Safety

Confirmed carcinogen with experimental carcinogenic, tumorigenic, and teratogenic data. Mildly toxic by ingestion. Human systemic effects by ingestion: dermatitis and androgenic effects. Human teratogenic effects: developmental abnormalities of the musculoskeletal system and urogenital system; and behavioral effects in the newborn. Human reproductive effects: spermatogenesis; testes, epididymis, sperm duct changes; impotence; male breast development; other male effects; ovaries, fallopian tube changes; menstrual cycle changes or disorders; uterus, cervix, vagina effects; postpartum effects; changes in female fertility. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

5.8 Specification

The 19-Norethisterone with the cas number 68-22-4, is also called (8R,9S,10R,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one. Its' system names are (1)19-Nor-17-alpha-pregn-4-en-20-yn-3-one, 17-hydroxy-; (2)19-Nor-17alpha-pregn-4-en-20-yn-3-one, 17-hydroxy- (8CI); (3)19-Norpregn-4-en-20-yn-3-one, 17-hydroxy-, (17alpha)-; (4)Norethisterone. And it belongs to the following product categories: (1)Active Pharmaceutical Ingredients; (2)Acetylenes; (3)Biochemistry; (4)Functionalized Acetylenes; (5)Hydroxyketosteroids; (6)Steroids; (7)Intermediates & Fine Chemicals; (8)Pharmaceuticals. It seems like off-white to pale yellow solid.

Physical properties about 19-Norethisterone are: (1)ACD/LogP: 3.38 ; (2)# of Rule of 5 Violations: 0 ; (3)ACD/LogD (pH 5.5): 3.38 ; (4)ACD/LogD (pH 7.4): 3.38 ; (5)ACD/BCF (pH 5.5): 219.89 ; (6)ACD/BCF (pH 7.4): 219.89 ; (7)ACD/KOC (pH 5.5): 1652.54 ; (8)ACD/KOC (pH 7.4): 1652.54 ; (9)#H bond acceptors: 2 ; (10)#H bond donors: 1 ; (11)#Freely Rotating Bonds: 1 ; (12)Polar Surface Area: 26.3??2 ; (13)Index of Refraction: 1.577 ; (14)Molar Refractivity: 85.55 cm3 ; (15)Molar Volume: 258 cm3 ; (16)Polarizability: 33.91 ×10-24cm3 ; (17)Surface Tension: 49 dyne/cm ; (18)Density: 1.15 g/cm3 ; (19)Flash Point: 190.5 °C ; (20)Enthalpy of Vaporization: 81.38 kJ/mol ; (21)Boiling Point: 447 °C at 760 mmHg ; (22)Vapour Pressure: 7.22E-10 mmHg at 25°C

Uses of 19-Norethisterone: It is used in some combined oral contraceptive pills and in some progestogen only pills. It is a progestogen and can be used to treat premenstrual syndrome, painful periods, abnormal heavy bleeding, irregular periods, menopausal syndrome (in combination with oestrogen), or to postpone a period.

When you are using this chemical, please be cautious about it as the following: It is not only irritating to eyes, respiratory system and skin but also harmful by inhalation, in contact with skin and if swallowed. And it shows limited evidence of a carcinogenic effect. Before you are using it, you would better wear suitable protective clothing, gloves and eye/face protection to avoid breathing dust. In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.).

You can still convert the following datas into molecular structure :
(1).SMILES: O=C4\C=C3/[C@@H]([C@H]2CC[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)C)CC4
(2).InChI:InChI=1/C20H26O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,12,15-18,22H,4-11H2,2H3/t15-,16+,17+,18-,19-,20-/m0/s

Toxic information of 19-Norethisterone can be showed as follows:

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
mouse LD50 oral 6gm/kg (6000mg/kg) ? Drugs in Japan Vol. -, Pg. 809, 1990.
women TDLo oral 42mg/kg (42mg/kg) ENDOCRINE: ANDROGENIC

SKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE"
American Journal of Obstetrics and Gynecology. Vol. 84, Pg. 962, 1962.

5.9 Toxicity
LD50 oral in mouse: 6gm/kg
5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Carcinogenicity, Category 2

Reproductive toxicity, Category 1A

Reproductive toxicity, Additional category for effects on or via lactation

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word

Danger

Hazard statement(s)

H351 Suspected of causing cancer

H360 May damage fertility or the unborn child

H362 May cause harm to breast-fed children

Precautionary statement(s)
Prevention

P201 Obtain special instructions before use.

P202 Do not handle until all safety precautions have been read and understood.

P280 Wear protective gloves/protective clothing/eye protection/face protection.

P260 Do not breathe dust/fume/gas/mist/vapours/spray.

P263 Avoid contact during pregnancy and while nursing.

P264 Wash ... thoroughly after handling.

P270 Do not eat, drink or smoke when using this product.

Response

P308+P313 IF exposed or concerned: Get medical advice/ attention.

Storage

P405 Store locked up.

Disposal

P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

9. Other Information
9.0 Merck
6697
9.1 BRN
1915671
9.2 Description
Norethindrone is a progestin (a synthetic substance with properties similar to progesterone) that is best known as the first female oral contraceptive, or the “pill.”Norethindrone’s global impact on society and culture has made it one of the most important inventions in history.
9.3 Chemical Properties
Off-White to Pale Yellow Solid
9.4 Originator
Norlutin,Parke Davis ,US,1957
9.5 History
The development of norethindrone as a female oral contraceptive took place indirectly over 30 years as a result of steroid research.This research accelerated in the 1930s when structures and medical applications of steroidal compounds were determined.Steroids are lipids, which include cholesterol, bile salts,and sex hormones,that are characterized by a structure of three fused six-carbon rings and a five-carbon ring.
In 1957, both norethindrone and norethynodrel were approved by the Food and Drug Administration (FDA) for treating menstrual problems and infertility. In 1960, the FDA approved Searle's norethynodrel under the trade name Enovid. Norethindrone was approved as an oral contraceptive in 1962 under the trade name Ortho-Novum.
9.6 Uses
Progestin contraceptives work by producing pregnant-like conditions in a female to preventovulation.During pregnancy, progesterone is released by the placenta during development ofthe fetus.This in turn suppresses development of egg follicles and ovulation. Progestins mimicthis condition and thus prevent or delay ovulation.Oral contraceptives currently use progestinand estrogen in combination to prevent ovulation and thicken cervical mucus.The latter makeit harder for sperm to enter the uterus and for an egg to implant on the uterine wall.
9.7 Uses
progestogen
9.8 Uses
A synthetic progestin
9.9 Uses
Progesteron. Norethindrone and acetate in combination with estrogen as contraceptive (oral). It is reasonably anticipated to be a human carcinogen
9.10 Definition
ChEBI: A 17beta-hydroxy steroid that is testosterone in which the hydrogen at position 17 is replaced by an ethynyl group and in which the methyl group attached to position 10 is replaced by hydrogen.
9.11 Manufacturing Process
7.5 grams of 3-methoxyestrone were dissolved in 750 cc of anhydrous dioxane in a three-neck flask, placed in a box and insulated with cotton wool. 2 liters of anhydrous liquid ammonia and 15 grams of lithium metal in the form of wire were added to the mechanically stirred solution. After stirring for one hour, 150 cc of absolute ethanol were added at such speed that no bumping occurred; when the blue color had disappeared, 500 cc of water were added in the same way. The ammonia was evaporated on the steam bath and the product collected with 2 liters of water. It was extracted with ether and then with ethyl acetate and the combined extract was washed to neutral and evaporated to dryness under vacuum, leaving 7.4 grams of a slightly yellow oil.
The oil thus obtained was dissolved in 400 cc of methanol and refluxed during one hour with 150 cc of 4N hydrochloric acid. The mixture was poured into a sodium chloride solution and extracted with ethyl acetate, washed to neutral, dried and evaporated to dryness. The product was a yellow oil which showed an ultraviolet absorption maximum characteristic of a ?4-3-ketone.
A solution of 2.7 grams of chromic acid in 20 cc of water and 50 cc of acetic acid was added to the stirred solution of the above oil in 100 cc of acetic acid, maintaining the temperature below 20°C. After 90 minutes standing, 50 cc of methanol were added and the mixture concentrated under vacuum (20 mm). The residue was extracted with ether, washed to neutral and evaporated to dryness. The residual semicrystalline product (7 grams) was chromatographed over alumina and the fractions eluted with ether yielded 3.2 grams of ?4-19norandrosten-3,17-dione having a MP of 163° to 167°C.
A solution of 2 grams of ?4-19-norandrosten-3,17-dione and 0.4 gram of pyridine hydrochloride in 50 cc of benzene free of thiophene was made free of moisture by distilling a small portion; 4 cc of absolute alcohol and 4 cc of ethyl orthoformate were added and the mixture was refluxed during 3 hours. 5 cc of the mixture were then distilled and after adding an additional 4 cc of ethyl orthoformate the refluxing was continued for 2 hours longer. The mixture was evaporated to dryness under vacuum and the residue was taken up in ether, washed, dried and evaporated to dryness. The residue was crystallized from hexane-acetone and then from ether to give ?3,5-19-nor-3ethoxy-androstadien-17-onewith a MP of 140° to 142°C.
One gram of potassium metal was dissolved in 25 cc of tertiary amyl alcohol by heating under an atmosphere of nitrogen. One gram of ?3,5-19-nor-3ethoxyandrostadien-17-onein 25 cc of anhydrous toluene was added and nitrogen was passed during 15 minutes. Then acetylene (especially dried and purified) was passed during 14 hours through the mechanically stirred solution, at room temperature.
The mixture was poured in water, acidified to pH 1 with dilute hydrochloric acid, heated on the steam bath for 30 minutes and then subjected to steam distillation to remove the organic solvents. The residue was filtered, dried and recystallized several times from ethyl acetate. The ?4-19-nor-17αethinylandrosten-17β-ol-3-onethus obtained had a MP of 198° to 200°C (in sulfuric acid bath), 200° to 204°C (Kofler).
9.12 Brand name
Camila (Barr); Errin (Barr); Micronor (OrthoMcNeil); Nor-QD (Watson); Norlutin (Parke-Davis).
9.13 Therapeutic Function
Progestin
9.14 General Description
Norethindrone, 17α-ethinyl-19-nortestosterone, and itsΔ5(10)-isomer, norethynodrel, might appear at first glance tobe subtle copies of each other. One would predict that theΔ5(10)-double bond would isomerize in the stomach’s acid tothe Δ4-position. However, the two drugs were actually developedsimultaneously and independently; hence, neither can beconsidered a copy of the other. Furthermore, norethindrone isabout 10 times more active than norethynodrel, indicating that isomerization is not as facile in vivo asone might predict. Although they are less active than progesteronewhen given subcutaneously, they have the importantadvantage of being orally active. The discovery of the potentprogestin activity of 17α-ethinyltestosterone (ethisterone) and19-norprogesterone preceded the development of these potentprogestins. Both are orally active, with the 17α-ethinyl groupblocking oxidation to the less active 17-one. The rich electrondensity of the ethinyl group and the absence of the 19-methylgroup greatly enhance progestin activity. Both compoundswere of great importance as progestin components of oralcontraceptives, although currently, use of norethynodrel isminimal. Norethindrone, USP, and norethindrone acetate,USP, are widely used for all the usual indications of the progestins,as well as being components of oral contraceptives.Because these compounds retain key features of the testosteronestructure, including the 17β-OH, it is not surprisingthat they possess some androgenic side effects.
9.15 Biochem/physiol Actions
19-norethindrone is an oral contraceptive involved in the inhibition of cytosolic sulfotransferases (SULT).
9.16 Safety Profile
Confirmed carcinogen with experimental carcinogenic, tumorigenic, and teratogenic data. Mddly toxic by ingestion. Human systemic effects by ingestion: dermatitis and androgenic effects. Human teratogenic effects: developmental abnormalities of the musculoskeletal system and urogenital system; and behavioral effects in the newborn. Human reproductive effects: spermatogenesis; testes, epididymis, sperm duct changes; impotence; male breast development; other male effects; ovaries, fallopian tube changes; menstrual cycle effects; postpartum effects; changes in female fertility. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.
9.17 Mesh
Oral contraceptives which owe their effectiveness to synthetic preparations. (See all compounds classified as Contraceptives, Oral, Synthetic.)|Oral contraceptives which owe their effectiveness to hormonal preparations. (See all compounds classified as Contraceptives, Oral, Hormonal.)
9.18 Mesh Entry Terms
19-Norpregn-4-en-20-yn-3-one, 17-hydroxy-, (17alpha)-
9.19 Chemical Synthesis
Norethindrone, 17α-ethynyl-17β-hydroxyestra-4-en-4-one (28.3.12), is made from 19-nor-4-androsten-3,17-dione (28.3.10), which is in turn synthesized by partial reduction of the aromatic region of the 3-O-methyl ether of estrone with lithium in liquid ammonia, and simultaneously of the keto-group at C17 to and hydroxyl group, which is then oxidized back to a keto-group by chromium (VI) oxide in acetic acid. The conjugated with the double bond carbonyl group at C3 is then transformed to dienol ethyl ether (28.3.11) using ethyl orthoformate. The obtained product is ethynylated by acetylene in the presence of potassium tert-butoxide. After hydrochloric acid hydrolysis, of the formed O-potassium derivative, during which the enol ether is also hydrolyzed, and the remaining double bond is shifted, the desired norethindrone (28.3.12) is obtained.

9.20 Carcinogenicity
Norethisterone is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
9.21 Environmental Fate
Waste streams from manufacturing plants producing contraceptives containing norethisterone can be sources of its release to the environment. If released to the air, norethisterone exists in both vapor and particulate phases in the atmosphere as deduced from a vapor pressure of 3.1× 10-7mmHg at 20 ℃. This vapor pressure indicates that norethisterone is not expected to be volatile from dry soil surfaces. Furthermore, based on an estimated Henry’s law constant of 5.8×10-10 atm m3 mol-1 for norethisterone, volatilization from water and moist soil surfaces is not plausible.
In aquatic systems, norethisterone is expected to adsorb to suspended solids and sediments given by its Koc value (soil organic carbon–water partitioning coefficient) of 220.
In the air, the vapor phase of norethisterone can be degraded by reaction with photochemically produced hydroxyl radicals with an estimated half-life of 1.1 h; the particulate phase can be removed by wet or dry deposition. Norethisterone is likely susceptible to photolysis by sunlight because of the presence of chromophores that absorb at wavelengths more than 290 nm. Hydrolysis of norethisterone is not anticipated under environmental conditions because of the lack of a functional group to hydrolyze.
In terrestrial systems, the Koc value of 220 suggests that norethisterone has moderate mobility in soil.
An estimated bioconcentration factor (BFC) of 42 for norethisterone indicates that its potential for bioconcentration in aquatic organisms is moderate.
9.22 Toxicity evaluation
As a synthetic progestin, norethisterone enters the target cells by passive diffusion and binds to its intracellular receptor to initiate transcription and protein synthesis. It changes the cervical mucus so that sperm migration or implantation of the fertilized ovum in the uterus is inhibited. Repeated low doses of norethisterone can change the rate of ovum transport by affecting motility and secretion in the fallopian tubes. When administered at high doses, norethisterone can suppress ovulation and cause ovarian and endometrial atrophy. Variable suppression of follicle stimulating hormone (FSH) and luteinizing hormone (LH) occurs with low doses.
10. Computational chemical data
  • Molecular Weight: 298.41924g/mol
  • Molecular Formula: C20H26O2
  • Compound Is Canonicalized: True
  • XLogP3-AA: null
  • Exact Mass: 298.193280068
  • Monoisotopic Mass: 298.193280068
  • Complexity: 594
  • Rotatable Bond Count: 1
  • Hydrogen Bond Donor Count: 1
  • Hydrogen Bond Acceptor Count: 2
  • Topological Polar Surface Area: 37.3
  • Heavy Atom Count: 22
  • Defined Atom Stereocenter Count: 6
  • Undefined Atom Stereocenter Count: 0
  • Defined Bond Stereocenter Count: 0
  • Undefined Bond Stereocenter Count: 0
  • Isotope Atom Count: 0
  • Covalently-Bonded Unit Count: 1
  • CACTVS Substructure Key Fingerprint: AAADceB4MAAAAAAAAAAAAAAAAAAAAYAAAAAwYIAAAAAAAGDAAAAAGgAACAAAD0SAgAACAAAAAgDIGqBSAAgAAAAgAAAACAEAAEgAABIAAQAAQAAEgAAIAQOIyPCPgAAAAAAAAACAAAQAACAAAYAADAAAAA==
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  • Products:Pharmaceutical raw materials,Chemical reagent, Food aditives,Plant ExtracPharmaceutical and pesticide intermediates.
  • Tel:86-431-81915458
  • Email:cathytan@jltely.com
19-Norpregn-4-en-20-yn-3-one,17-hydroxy-, (17a)-
  • Purity:99%Packing: 200kg/bag FOB
  • Price: 1 USD/gram
  • Time: 2022/11/30
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  • Products:1451-82-7 236117-38-7 49851-31-2 124878-55-3 20388-87-8 22374-89-6 28578-16-7 52190-28-0 2836-82-0 288573-56-8 20320-59-6
  • Tel:+86-311-8985004
  • Email:rhea@zk-chem.com
Norethindrone CAS:68-22-4,white to off-white powder
  • Purity:99%Packing: 200kg/bag FOB
  • Price: 32 USD/g
  • Time: 2022/11/18
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  • Products:chemical raw materials, veterinary drug raw materials, animal and plant extracts, pharmaceutical excipients, pharmaceutical products, food additives
  • Tel:86-155-03787326
  • Email:hnkanbeichemical@126.com
norethisterone
  • Purity:99%Packing: 200kg/bag FOB
  • Price: 1 USD/kilogram
  • Time: 2022/11/15
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  • Products:Cosmetic Raw Materials,solvents,etc.
  • Tel:86-311-66562153
  • Email:breeduan@crovellbio.com
norethisterone Cas 68-22-4 from China
  • Purity:99%Packing: 200kg/bag FOB
  • Price: 10 USD/kilogram
  • Time: 2022/11/08
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